Disrupting CD38-driven T cell dysfunction restores sensitivity to cancer immunotherapy.

A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD) catabolism, is highly expressed in exhausted CD8 T cells in melanoma and is associated with ICB resistance.

Mobilization of innate and adaptive antitumor immune responses by the RNP-targeting antibody ATRC-101.

Immunotherapy approaches focusing on T cells have provided breakthroughs in treating solid tumors. However, there remains an opportunity to drive anticancer immune responses via other cell types, particularly myeloid cells. ATRC-101 was identified via a target-agnostic process evaluating antibodies produced by the plasmablast population of B cells in a patient with non-small cell lung cancer experiencing an antitumor immune response during treatment with checkpoint inhibitor therapy.

Quantitative proteome-based guidelines for intrinsic disorder characterization.

Intrinsically disordered proteins fail to adopt a stable three-dimensional structure under physiological conditions. It is now understood that many disordered proteins are not dysfunctional, but instead engage in numerous cellular processes, including signaling and regulation. Disorder characterization from amino acid sequence relies on computational disorder prediction algorithms.

Villification in the mouse: Bmp signals control intestinal villus patterning.

In the intestine, finger-like villi provide abundant surface area for nutrient absorption. During murine villus development, epithelial Hedgehog (Hh) signals promote aggregation of subepithelial mesenchymal clusters that drive villus emergence. Clusters arise first dorsally and proximally and spread over the entire intestine within 24 h, but the mechanism driving this pattern in the murine intestine is unknown.

A Two-Dimensional Multiphase Model of Biofilm Formation in Microfluidic Chambers.

The bacterial pathogen Xylella fastidiosa is the causal agent of many pathological conditions of economically important agricultural crops. There is no known cure for X. fastidiosa diseases, and management of the problem is based solely in controlling the population of insect vectors, which is somewhat effective.

Surveying the floodgates: estimating protein flux into the endoplasmic reticulum lumen in Saccharomyces cerevisiae.

Endoplasmic reticulum resident proteins, along with all proteins traveling through the secretory pathway must enter endoplasmic reticulum lumen through membrane-embedded translocons. In Saccharomyces cerevisiae the heterotrimeric endoplasmic reticulum translocon is composed of the Sec61p, Sss1p, and Sbh1p core subunits. While the involvement of various molecules associated with the Sec61 complex has been thoroughly characterized, little attention has been given to the overall flux through these channels.

Competitive inhibition reaction mechanisms for the two-step model of protein aggregation.

We propose three new reaction mechanisms for competitive inhibition of protein aggregation for the two-step model of protein aggregation. The first mechanism is characterized by the inhibition of native protein, the second is characterized by the inhibition of aggregation-prone protein and the third mechanism is characterized by the mixed inhibition of native and aggregation-prone proteins. Rate equations are derived for these mechanisms, and a method is described for plotting kinetic results to distinguish these three types of inhibitors.

Pattern formation exhibited by biofilm formation within microfluidic chambers.

This article investigates the dynamics of an important bacterial pathogen, Xylella fastidiosa, within artificial plant xylem. The bacterium is the causative agent of a variety of diseases that strike fruit-bearing plants including Pierce's disease of grapevine. Biofilm colonization within microfluidic chambers was visualized in a laboratory setting, showing robust, regular spatial patterning.

Marginal stability and traveling fronts in two-phase mixtures.

Mixtures of materials that move relative to each other arise in a variety of applications, especially in biophysical problems where the mixture consists of materials with different material properties. The variety of applications leads to a bewildering array of multiphase models, each with slightly different behaviors and interpretations, depending on the application. Some of the behaviors include phase separation, traveling waves, and linear instabilities.